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The proximal tubules\u2019 reliance on fatty acid oxidation rather than glycolysis underscores their unique metabolic profile, consistent with the absence of key glycolytic enzymes. This dysregulation contributes to maladaptive hypertrophy in CKD, where surviving nephrons exhibit compensatory hypertrophy to maintain kidney function. Here, we focus on two key regulators of lipid metabolism: peroxisome proliferator\u2013activated receptor alpha (PPAR\u03b1) and adenosine monophosphate (AMP)-activated protein kinase (AMPK). Recent multi-omics studies have identified PPAR\u03b1 as an important determinant of proximal tubule cell size and a mediator of compensatory hypertrophy. In CKD models, AMPK activity decreases, impairing cellular responses to energy stress, as indicated by altered AMP\/ATP ratios. This defective energy sensing may be exacerbated by uremic metabolites that diminish AMPK function. Unc-51-like autophagy activating kinase 1 (ULK1) has been identified as a regulator of AMPK activity through specific phosphorylation sites that enhance AMP sensitivity. Future research should assess whether targeting these pathways restores metabolic homeostasis and mitigates CKD progression by enhancing AMPK activity and lipid metabolism.<\/jats:p>","DOI":"10.1007\/s10157-026-02923-9","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T11:16:15Z","timestamp":1785842175000},"page":"1261-1269","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Energy metabolism in the kidney and its role in chronic kidney disease"],"prefix":"10.1007","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7722-4131","authenticated-orcid":false,"given":"Hiroaki","family":"Kikuchi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Tsuboya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinming","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari","family":"Sugimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miyu","family":"Yoshikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maho","family":"Usui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takefumi","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Knepper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichi","family":"Uchida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eisei","family":"Sohara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"2923_CR1","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1038\/ki.1986.5","volume":"29","author":"JJ Cohen","year":"1986","unstructured":"Cohen JJ. 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